PXD068916-1

PXD068916 is an original dataset announced via ProteomeXchange.

Title	USP52 mediated deubiquitylation of RAB11FIP5 inhibits transferrin recycling to promote ferroptosis resistance in HNSCC
Description	Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, functions as an innate tumor suppression mechanism. However, the regulatory networks governing ferroptosis sensitivity in cancer cells remain incompletely elucidated. In this study, we identify RAB11FIP5 as a novel negative regulator of ferroptosis in head and neck squamous cell carcinoma (HNSCC) cells. Mechanistically, RAB11FIP5 competitively binds to RAB11A against RAB11FIP1, thereby inhibiting the recycling of transferrin (TF) and transferrin receptor (TFR), which are critical for cellular iron import. Furthermore, we demonstrate that USP52 acts as a deubiquitinase that stabilizes RAB11FIP5 by removing the K48 ubiquitin chains in ferroptosis-resistant HNSCC cells. In a subcutaneous xenograft model, knockout of RAB11FIP5 not only enhances the anti-tumor efficacy of the ferroptosis inducer IKE but also suppresses HNSCC tumor growth even in the absence of IKE treatment. Analysis of public databases and patient tissue samples reveals that high RAB11FIP5 expression in HNSCC tumors correlates with poor prognosis. Collectively, our findings elucidate a previously unrecognized mechanism by which RAB11FIP5 regulates ferroptosis through modulating TF/TFR recycling, highlighting its potential as both a prognostic marker and a therapeutic target for HNSCC.
HostingRepository	iProX
AnnounceDate	2025-09-28
AnnouncementXML	Submission_2026-03-31_17:14:47.528.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anjiang Sun
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-28 18:06:28	ID requested
⏵ 1	2026-03-31 17:14:48	announced

Dataset with its publication pending

submitter keyword: Ferroptosis, HNSCC, RAB11FIP5, RAB11FIP1

Juan Lin
contact affiliation	School of Medicine, Xiamen University
contact email	linjuan2020@xmu.edu.c
lab head
Anjiang Sun
contact affiliation	School of Medicine, Xiamen University
contact email	sunanjiang0601@foxmail.com
dataset submitter

iProX dataset URI